Michiko Ichimasa

Cutting Edge: Agonistic Effect of Indomethacin on a Prostaglandin D2 Receptor, CRTH2

Indomethacin is a widely used nonsteroidal anti-inflammatory drug and is generally known to exhibit its multiple biological functions by inhibiting cyclooxygenases or activating peroxisome proliferator-activated receptors. In this study, we present evidence demonstrating that the novel PGD2 receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) is another functional target for indomethacin. Indomethacin induced Ca2+ mobilization in CRTH2-transfected K562 cells at submicromolar concentrations (approximate EC50, 50 nM) in a Gαi-dependent manner as PGD2 did. Other nonsteroidal anti-inflammatory drugs (aspirin, sulindac, diclofenac, and acemetacin) had no such effect even at micromolar concentrations. In chemotaxis assay, three CRTH2-expressing cell types, Th2 cells, eosinophils, and basophils, were all significantly attracted by indomethacin (EC50, 50–500 nM) as well as by PGD2 (EC50, 2–20 nM), and the effects of indomethacin were blocked by anti-CRTH2 mAb. These results suggest the involvement of CRTH2 in mediating some of therapeutic and/or unwanted side effects of indomethacin, independently of cyclooxygenases and peroxisome proliferator-activated receptors.

Conversion Rate of HTO to OBT in Plants

ABSTRACT The conversion rate of tritiated water (HTO) in plants’ leaves to organically bound tritium (OBT) in their edible parts in the open air was obtained for several vegetables (komatsuna, radish and cherry tomato) during a chronic tritiated hydrogen (HT) release experiment at Chalk River in 1994. During the experiment, HT gas was continuously released to the atmosphere at the cultivated site for 12 days, and HTO and OBT concentrations in cultivated plants were measured. For plants’ leaves, the conversion rate of HTO to OBT was about 0.2 (% hr−1), but it varied with their growth stage. A chamber experiment was also carried out in laboratory for comparison. The chamber experiment results showed that the conversion rate under artificial lights was half that in the field experiment.

Re-emission of heavy water vapour from soil to the atmosphere.

The re-emission process of tritiated water (HTO) deposited on a soil surface is an important process to assess tritium doses to the general public around nuclear fusion facilities in future. A field experiment using heavy water (HDO) as a substitute for HTO was carried out in the summertime to investigate the re-emission process of HTO from soil to the atmosphere. In the experiment, the time variations of depth profiles of HDO concentrations in soil exposed to HDO vapour and soil mixed with HDO were measured during the re-emission process on the field. The HDO concentrations in soil water in top soil layers of both the exposed and mixed soil rapidly decreased with time during the re-emission. However, the decrease of exposed soil was much greater than that of mixed soil. The re-emission process was analysed using a model including the evaporation of HDO from soil, the exchange between soil HDO and air H2O, and the diffusion of HDO in soil. It was found that the model is applicable to calculating the time variations of detailed depth profiles of HDO concentration in soil water in surface soil layers, using an estimated exchange velocity.

The JCO criticality accident at Tokai-mura, Japan: An overview of the sampling campaign and preliminary results

A criticality accident occurred on September 30, 1999 at the uranium conversion facility of the JCO Company Ltd. in Tokai-mura, Japan. A collaborating scientific investigation team was organized in two groups, the first to carry out research on the environmental impact (the environmental research group) and the second to assess the radiation effects on residents (the biological research group). This report concerns only the activities of the environmental research group. Four investigative teams were sent on different dates to the accident site and its vicinity to collect samples. About 400 samples were collected and subjected to analysis. An outline of the sampling campaign is presented here along with a brief chronology of the accident and the preliminary key results obtained by the independent research group are summarised in this Special Issue of the Journal of Environmental Radioactivity.

HT Oxidation in Soils in Ibaraki and Isolation, Identification of HT Oxidizing Soil Bacteria

ABSTRACT The distribution of molecular tritium (HT) oxidation activity and HT oxidizing bacteria in 5-cm soil sections from the surface to 20 cm depth in natural and cultivated fields in Mito was determined in in vitro experiments. HT oxidation activity was the highest in the top section of the natural soil, about twice that of the top section of the cultivated soil, and decreased with depth. From the natural and cultivated soil sections, 195 and 969 isolated strains with HT oxidation activity were obtained, respectively. The distribution profile of the occurrence rate and the sum of oxidation activity of HT oxidizing bacteria in each soil section were consistent with that of HT oxidation activity in the soil section. Most of the HT oxidizing isolates, 84% for the natural soil and 94% for the cultivated soil, were actinomycetes, Gram-positive bacteria.

Tritium Elimination System Using Tritium Gas Oxidizing Bacteria

In order to eliminate atmospheric tritium gas (HT) released from tritium handling apparatus, we proposed to use the HT oxidizing ability (hydrogenase enzyme) of bacterial strains isolated from surface soils instead of a high temperature precious metal catalyst. Among the isolated strains with high HT oxidation activity, several strains were selected to develop a tritium elimination (detritiation) system. Bioreactors were made of bacterial cells grown on agar medium on a cartridge filter and stored in a refrigerator until use. The detritiation ability of these bioreactors at room temperature was investigated during the intentional HT release experiments carried out in the Cassion Assembly for Tritium Safety Study (CATS) in TPL/JAERI. When HT contaminated air from the CATS was introduced into the biological detritiation system, in which three bioreactors were connected in series, 86% of HT in air was removed as tritiated water in these bioreactors at a flow rate of 100 cm3/min for 2 hours.

Formation and retention of organically bound deuterium in rice in deuterium water release experiment.

As a substitute of tritium, deuterated water (D2O) vapor release experiments were performed in a greenhouse to estimate the different formation and subsequent retention of organically bound deuterium in rice plants between daytime and nighttime exposure. Potted rice plants were exposed to D2O vapor in the greenhouse for 8 h, under day or night conditions. Deuterium concentrations in free water and organic matter in rice leaves and ears were investigated until harvest time. The formation of organically bound deuterium in the daytime was higher than during the nighttime by the factors of 2.4 for the ear and 2.9 for the leaf. The decrease of the organically bound deuterium concentration in the ear after the nighttime exposure was faster than that after the daytime exposure. Data analysis was carried out using a compartment model in which different generating processes of organic matter were considered. The calculated organically bound deuterium retention in rice agreed with the measured value.

Studies of mutagenesis caused by low dose rate tritium radiation using a novel hyper-sensitive detection system

ABSTRACT A novel hyper-sensitive detection system was developed to detect Hprt-deficient mutations using Hprt deficient hamster fibroblast cells which carry a normal human X-chromosome. The system has been found to be 100-fold more sensitive for detecting mutations than the conventional system which uses an internal Hprt gene. The mutation frequency induced by 1 Gy of tritium radiation at different dose rates (0.9, 0.4, 0.04, and 0.018 Gy/h) was measured. No significant differences in mutation frequencies were observed within the range of dose rates used, suggesting that if a reverse dose-rate effect exists, it may not be observable with tritium radiation at dose rates over 0.018 Gy/h. Interestingly, molecular analysis of the Hprt locus in Hprt-deficient mutants induced by tritium showed that deletion sizes observed in the hamster cell’s human X-chromosome under these conditions are much smaller in cells exposed at 0.04 (and 0.018 Gy/h) than in cells exposed at 0.9 Gy/h. This phenomenon seems to be specific for tritium radiation because it was not apparent after exposure to γ-rays. The novel hyper-sensitive detection system used here is useful for analysis of the mutagenic effects of low doses of tritium radiation delivered at low dose rates.

Organically bound deuterium in rice and soybean after exposure to heavy water vapor as a substitute for tritiated water

ABSTRACT Heavy water vapor release experiments were carried out in a greenhouse using deuterium as a substitute for tritium and uptake and loss kinetics of D2O in leaves and formation, translocation and retention of organically bound deuterium (OBD) in rice and soybean were investigated. Rate constants of D2O uptake in leaves of rice plant and soybean in the daytime release were 2.4 and 3.0 hr−1, respectively, and 5-4 times higher than those in the nighttime release. Rate constants of D2O loss in leaves after daytime release were about twice those after the nighttime release. The half time of D2O loss was 0.6–0.7 hr for leaves of rice plant and soybean. After D2O release, OBD concentration in unhulled rice and soybean increased with time until 4 –5 days of the experiments and then decreased with time and the extent of decrease was remarkable in soybean pea.

Uptake of heavy water and loss by tangerine in the heavy water vapor release experiment in a greenhouse as a substitute for tritiated water

Heavy water (D2O) vapor release experiments were carried out in a greenhouse using deuterium as a substitute for tritium and uptake and loss kinetics of D2O in leaf of a tangerine tree and formation, translocation and retention of organically bound deuterium (OBD) in tangerine exposed to D2O under different growth stage were investigated. Rate constants of D2O uptake in leaves of tangerine were 0.2-1.11 hr-1 in the daytime release and 0.03-0.12 hr-1 in the nighttime release. Rate constants of D2O loss in leaf after daytime release were almost the same as those after the nighttime release. No significant differences in the half time of D2O loss were observed between daytime and nighttime releases, but those in winter experiments were about 6 times higher than those in summer ones. The retention of OBD of the edible part of tangerine at harvest was very low and OBD was 0.08% or 0.07% on average of D2O in air moisture in daytime or nighttime releases.